In the next year research will be concentrated along two major lines: 1) Chemical synthesis of VL and its association with native VH to form an active Fv. More precise analysis of the association between native VL and VH will be conducted. Certain improvements in the chemical synthesis according to Merrifield will be introduced. The synthetic VL will be characterized by various chemical and physical methods. Finally, after purification of the product, experiments will be conducted to associate it with native VH. This will be the first step towards chemical synthesis of an antibody. 2) Extensive research will be conducted towards elucidation of the three-dimensional structure in solution of the Fv combining site. These studies will be based on the model of Fv 315 that was recently built by us. Various ligands with different "reporter" groups will be used. Modifications of known residues in the Fv site will help to define reference points for obtaining three-dimensional coordinates of various residues at the site.